The number of end-stage kidney disease (ESKD) patients in need of dialysis or transplantation has been increasing all over the world. During the 10 years from 1990 to 2000, the number of ESKD patients increased from 430,000 to 1,065,000. In 2008, the number reached at least about 1,650,000. In 2011, the number of patients receiving maintenance dialysis reached approximately 300,000 in Japan. This means that the number of patients per million people is 2,126, which is the second-highest such figure in the world. Chronic kidney diseases (CKDs) are preliminary forms of ESKDs that have been increasing all over the world. The number of CKD patients in the U.S. in 2000 was estimated to account for 13.07% (25,610,000 individuals) of the adult population. The number of CKD patients in Japan in 2005 accounted for 12.9% (13,300,000 individuals) of the adult population. The number of CKD patients and patients with preliminary forms of CKDs is said to have reached as high as 20,000,000. In addition, CKDs are risk factors for cardiovascular diseases (CVDs). In Western countries, the number of CKD patients who die due to CVDs is greater than the number of CKD patients who start dialysis. Also in Japan, CKDs are risk factors for CVDs. Meanwhile, if each CKD patient could receive adequate treatment in accordance with his/her own disease state, it would be possible to significantly reduce the number of patients who start dialysis or die due to heart diseases. For such purpose, adequate evaluation methods are necessary. In the existing test methods, the glomerular filtration rate (GFR) can be used for accurate renal function assessment. The term “glomerular filtration rate” refers to the volume of serum filtered through all glomeruli of the kidneys per unit of time. A decline in the renal function due to renal failure or the like is associated with a decline in the filtration capacity of glomeruli. Therefore, the degree of deterioration of the renal function can be confirmed by determining GFR. In order to accurately determine GFR, inulin clearance measurement with the use of inulin is recommended. However, since inulin clearance measurement is complex, creatinine clearance based on the creatinine level and estimated glomerular filtration rate (eGFR) are used in clinical practice. In order to obtain the creatinine clearance or eGFR, it is necessary to obtain the serum creatinine level. Serum creatinine testing is invasive and thus imposes a significant burden on patients. That is, if GFR could be estimated in a non-invasive manner, it would be beneficial to patients.
Megalin in urine is a substance observed in association with renal diseases. Convenient renal disorder tests involving measurement of urinary megalin have been disclosed (Patent Documents 1 and 2).
Megalin also known as Glycoprotein 330 (gp330) or Low Density Lipoprotein (LDL)-receptor relate protein 2 (LRP2) is a glycoprotein having a molecular weight of about 600 kDa, which is expressed in renal proximal tubular epithelial cells (Non-patent Documents 1 and 2).
As a result of cell culture experiments using renal proximal tubular epithelial cells, the presence of two types of megalin, membrane-bound full length megalin and soluble-form megalin (fragment containing the extracellular domain) lacking the intracellular domain, is known (Non-patent Document 3). A method for measuring urinary full-length human megalin, the extracellular domain thereof, and the intracellular domain thereof has also been reported (Patent Document 3).